Low-intensity Hippocampal Transcranial Ultrasound Stimulation for Managing Cognitive and Sleep Dysfunction in Preclinical Alzheimer's Disease

NCT07298876 | Enrolling By Invitation

• 1 other identifier: 2024.652
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Sleep disturbances, as a common symptom, can jeopardize the brain health and cognitive function and even lead to cognitive impairments in older adults. The co-occurring sleep disturbances cognitive complaints can significantly affect brain functions, and even be implicated as a key contributing factor in the development of prodromal Alzheimer's disease (AD). At present, very few non-pharmacological therapies are developed for managing these comorbidities in older adults. Focused low-intensity transcranial ultrasound stimulation (TUS) enables to stimulation the deep brain structures, such as hippocampus, with optimized focality and specific frequency. Objectives: 1) To investigate the safety, feasibility and efficacy of a 2-week focused low-intensity hippocampal TUS on the severity of sleep disturbances and cognitive impairments in elderly patients; 2) to determine the sample size of a full-scale randomized clinical trial of low-intensity TUS in patients with preclinical AD; 3) to evaluate the effects of low-intensity TUS on the severity of sleep quality and cognitive functions at 2, 6 and 10 weeks after the treatments. Design: A 2-week randomized, double-blind, controlled clinical trial. Methods: Chinese right-handed preclinical AD patients with sleep disturbances (aged from 60 to 90 years) will be randomly assigned to a 2-week intervention of either low intensity TUS or sham TUS, with 10 participants per arm. Before intervention, T1-weighted magnetic resonance imaging (MRI) data is used to construct individual realistic head model. Comprehensive assessments, including sleep quality, cognitive performance and plasma p-tau217, Aß42 and Aß40 will be conducted at baseline, 2nd week, 6th week and 10th week. Program adherence and adverse effects will be monitored throughout intervention.

Conditions

Cognitive Impairment, Mild; Sleep Disturbances; Aging

Keywords

Sleep disturbances; Aging; Transcranial ultrasound stimulation; Hippocampus; Central Nervous System Diseases; Randomized clinical trial; Personalized medicine; Cognitive impairments; Glymphatic function

Outcome Measures

Primary Outcomes (2)

• Pittsburg Sleep Quality Index (PSQI)

  Description: The PSQI is a 19-item questionnaire that includes seven areas of subjective sleep quality and patterns in adults over the last month including the following components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, SDs, use of sleeping medications, and daytime dysfunction. Each item in the scale is scored from 0 to 3 scale (0 = no difficulty; 3 = severe difficulty). The scores are added to yield a global score ranging from 0 to 21 (0 = no difficulty; 21 = severe difficulties in all areas). This scale has good reliability and validity psychometrics and is widely used in research: Cronbach's alpha (0.77 to 0.83), sensitivity (89.6%), specificity (86.5%). Greater score of PSQI indicates worse sleep quality.

  10 weeks

• Delayed recall of the words

  Word-list learning test (WLLT), consisting of sixteen semantically non-associated words that is presented consecutively over three free trials of immediate recall, a 20-min delayed recall (to prevent recency effects). Delayed recall of the words derived from WLLT is used as a proxy for measuring working memory function.

  10 weeks

Secondary Outcomes (3)

• Objective sleep quality

  2 weeks

• The levels of plasma Aß

  10 weeks

• The levels of plasma tau

  10 weeks

Study Arms (2)

Active TUS

ACTIVE COMPARATOR

In active TUS group, participants will receive 500 kHz low-intensity TUS.

Device: Low-intensity transcranial ultrasound stimulation

Sham TUS

SHAM COMPARATOR

In sham TUS group, participants will receive sham TUS.

Device: Sham low-intensity transcranial ultrasound stimulation

Interventions

Low-intensity transcranial ultrasound stimulation DEVICE

Low-intensity TUS, as an advanced modality of transcranial brain stimulation, enables to stimulate the deep brain structures with optimized focality and specific frequency.

Active TUS

Sham low-intensity transcranial ultrasound stimulation DEVICE

Sham TUS uses the same settings as the active low-intensity TUS. During the sham treatment, the power will be off.

Sham TUS

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese, right-handed, aged from 60 to 85 years.
• Mild neurocognitive disorder due to Alzheimer's disease (NCD-AD) is identified with the Montreal Cognitive Assessment (MoCA) score range from 22 to 26.
• Sleep disturbances or poor sleep quality is assessed and defined with a total score of the Pittsburgh Sleep Quality Index (PSQI) greater than 5.
• No impairments in the activities of daily living.

You may not qualify if:

• Previous diagnosis of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease.
• History of neurological diseases including brain tumor, and stroke.
• History of psychiatric disorders including schizophrenia and depression.
• Presence of positive neurological diseases, such as stroke, brain tumor, dementia.
• Physically unable to attend the sessions of intervention.
• Currently enrolled in another intervention study.
• Currently taking a psychiatric or other medication that may affect sleep quality and cognition.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• The Hong Kong Polytechnic University: collaborator

Study Sites (1)

Tai Po Hospital

Hong Kong, Tai Po District, 100000, Hong Kong

Location

MeSH Terms

Conditions

Parasomnias; Cognitive Dysfunction; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 1, 2025
• First Posted: December 23, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): May 16, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)